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Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
LINC00680 modulates docetaxel resistance in breast cancer via the miR-320b/CDKL5 axis
Jia Li1,2, Jing Ke2, Cheng-Lin Qin3
1Department of Thyroid and Breast Surgery, 105860The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Abstract:
Introduction: Increasing evidence has indicated that LINC00680 represents an oncogenic factor in cancer; however, the mechanism by which LINC00680 contributes to breast cancer (BC) remains unknown. Methods: A dual-luciferase reporter assay was used to explore the relationship between LINC00680, miR-320b, and cyclin-dependent kinase 5 (CDKL5). A CCK-8 assay and transwell assay were utilized to evaluate the proliferation and invasion in docetaxel-resistant BC cells, respectively. Results: LINC00680 and CDKL5 protein levels were both upregulated when induced by different concentrations of docetaxel. LINC00680 knockdown decreased the expression level of drug resistance-related genes, proliferation, and invasion of BC cells. Bioinformatics prediction and dual-luciferase assays revealed that miR-320b targeted the 3'-unstranslated regions (UTR) of both LINC00680 and CDKL5, suggesting that the modulation of LINC00680 on CDKL5 occurred via sequestering miR-320b. Conclusion: Overall, this study highlights the important role of LINC00680 in docetaxel resistance through the miR-320b/CDKL5 pathway and provides a novel therapeutic strategy for BC drug resistance.
Insights
Long non-coding RNA LINC00680 promotes docetaxel resistance in breast cancer (BC) by regulating the miR-320b/CDKL5 pathway. This finding offers a potential new therapeutic strategy for overcoming BC drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- LINC00680 is increasingly recognized as an oncogenic factor in various cancers.
- The precise mechanism of LINC00680's role in breast cancer (BC) progression and drug resistance is not fully understood.
Purpose of the Study:
- To elucidate the mechanism by which LINC00680 contributes to docetaxel resistance in breast cancer.
- To investigate the regulatory relationship between LINC00680, miR-320b, and CDKL5 in BC cells.
Main Methods:
- Dual-luciferase reporter assays were employed to confirm the targeting relationship between LINC00680, miR-320b, and CDKL5.
- Cell Counting Kit-8 (CCK-8) and Transwell assays were used to assess cell proliferation and invasion.
- LINC00680 knockdown was performed to evaluate its effects on drug resistance-related genes.
Main Results:
- LINC00680 and Cyclin-Dependent Kinase 5 (CDKL5) protein levels were elevated in response to docetaxel.
- Knockdown of LINC00680 significantly reduced the proliferation and invasion of docetaxel-resistant BC cells.
- MiR-320b was identified as a direct target of both LINC00680 and CDKL5, indicating LINC00680 modulates CDKL5 via miR-320b sequestration.
Conclusions:
- LINC00680 plays a critical role in conferring docetaxel resistance in breast cancer.
- The miR-320b/CDKL5 pathway is a key mechanism through which LINC00680 promotes drug resistance.
- Targeting the LINC00680/miR-320b/CDKL5 axis presents a promising therapeutic avenue for overcoming docetaxel resistance in BC.
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